Her lover and employer, Jean Paulhan, had made the chauvinistic remark to her that no female was capable of writing an erotic novel. To prove him wrong, Desclos wrote a graphic, sadomasochistic novel that was published under the pseudonym Pauline Réage; in June of 1954. Titled Histoire d'O (Story of O), it proved Paulhan wrong and was an enormous, though controversial, commercial success. The book caused much speculation as to the identity of the author. Many doubted that it was a woman, let alone the demure, intellectual, and almost prudish persona depicted in Dominique Aury.

In addition, the book's graphic content sparked so much controversy that the following March the government authorities brought obscenity charges against the publisher and its mysterious author that were thrown out of court in 1959. However, a publicity ban and a restriction on the book's sale to minors was imposed by the judge. Following the lifting of the publicity ban in 1967 she published the conclusion to Story of O under the title Retour à Roissy, again using the pseudonym of Pauline Réage. According to her recent biography by Angie David, Desclos did not write this second novel.

She did an interview about erotic books in 1975 with author and publisher Régine Deforges, yet at the time her authorship of Story of O was still unknown. Desclos publicly admitted that she was the author of The Story of O forty years after the book was published, in an interview with The New Yorker magazine.